Biologic Therapies

Biologic therapies (sometimes called immunotherapy, biotherapy, or biologic response modifier therapy) do not target cancer cells directly but rather harness the immune system, either directly or indirectly, to fight cancer or to lessen the adverse effects that may be caused by some cancer treatments. Further, because cancer may develop when the immune system breaks down or is not functioning adequately, biologic therapies are designed to repair, stimulate, or enhance the immune system’s responses.

Cells in the immune system secrete 2 types of proteins: antibodies and cytokines. Cytokines are nonantibody proteins produced by some immune system cells to communicate with other cells. Types of cytokines include lymphokines, interferons, interleukins, and colony-stimulating factors. Some antibodies and cytokines, called biologic response modifiers, can be used in the treatment of cancer. Other biologic response modifiers include monoclonal antibodies, which can also be used to treat cancer, and vaccines.

Interleukins occur naturally in the body and can also be made in the laboratory. Many interleukins have been identified; interleukin-2 has been the most widely studied for use in cancer treatment. Interleukin-2 stimulates the growth and activity of many immune cells (eg, lymphocytes) that can destroy cancer cells. The FDA has approved interleukin-2 for the treatment of metastatic kidney cancer and metastatic melanoma.

Colony-stimulating factors (sometimes called hematopoietic growth factors) usually do not directly affect tumor cells but instead stimulate bone marrow production. Colony-stimulating factors allow doses of anticancer drugs to be increased without increasing the risk of infection or need for transfusion.

Monoclonal antibodies (mAbs) are produced by a single type of cell and are specific for a particular antigen. Researchers continue to examine ways to create mAbs that are specific for the antigens found on the surface of cancer cells being treated. Some examples of mAbs currently used in cancer treatment are rituximab and trastuzumab; note that the suffix for the names of all monoclonal antibodies is “-mab.”

Therapeutic mAbs are made by injecting human cancer cells into mice, which stimulates an antibody response. The cells producing antibodies are then removed and fused with laboratory-grown cells to create hybrid cells called hybridomas. Hybridomas can produce large quantities of these mAbs indefinitely.

Monoclonal antibodies have many potential uses in cancer treatment; for example, they could be linked to anticancer drugs, radioisotopes, other biologic response modifiers, or other toxins. When these antibodies attach to cancer cells, they are able to deliver these poisons directly to the cells. One example of this is ado-trastuzumab emtansine, which uses trastuzumab to deliver a cytotoxic microtubule inhibitor. Another is tositumomab radioconjugate, which delivers specifically targeted radiotherapy to tumors. Monoclonal antibodies carrying radioisotopes may also prove useful in the diagnosis of certain cancers, such as colorectal, ovarian, and prostate cancer.

Cancer treatment vaccines are being developed to help the immune system recognize cancer cells. These vaccines are designed to be injected after the disease is diagnosed rather than before it develops, in contrast to the vaccines against HPV or hepatitis B, which are aimed at cancer prevention. The cancer treatment vaccines may help the body reject tumors and prevent recurrence. The first treatment vaccine, which was approved in 2010, was customized to each patient for the treatment of metastatic prostate cancer. In 2015, an oncolytic virus treatment vaccine was approved to treat melanoma that cannot be surgically removed.

Other biologic approaches to cancer therapy include genetic profiling of certain tumors. Current management of lung cancer and melanoma is based on such profiling. Genetic profiling may also prove more helpful and effective than classifying tumors by their organ of origin. An example of this is the differentiation between those tumors with a normal tumor suppressor gene p53 from those with an abnormal tumor suppressor gene p53. Tumor cells with normal p53 genes are far more sensitive to chemotherapy than those with mutant p53.

• Dharmadhikari N, Mehnert JM, Kaufman HL. Oncolytic virus immunotherapy for melanoma. Curr Treat Options Oncol. 2015;16(3):326.

Ophthalmic considerations The eye and its adnexa are frequently involved in systemic malignancies as well as in extraocular malignancies that extend into ocular structures (including local malignancies of the skin, bone, and sinuses). Breast and lung cancers frequently metastasize to the eye and are the most common intraocular tumors in adults. Acute myelogenous and lymphocytic leukemias often have uveal and posterior choroidal infiltrates as part of their generalized disease. In children, these manifestations are often signs of central nervous system involvement and suggest a poor prognosis. Although malignant lymphomas do not usually involve the uveal tract, histiocytic lymphoma often involves the vitreous and presents as uveitis. The retina and choroid may also be involved.

Tumors of the eye and adnexa are discussed in several other BCSC volumes, including Section 4, Ophthalmic Pathology and Intraocular Tumors; Section 6, Pediatric Ophthalmology and Strabismus; Section 7, Oculofacial Plastic and Orbital Surgery; and Section 8, External Disease and Cornea.

• American Cancer Society website; www.cancer.org.

• European Society for Medical Oncology website; www.esmo.org.

• UpToDate; www.uptodate.com.

Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.